Eine unzureichende Erkennung und Beseitigung von sterbenden Zellen kann zur Entstehung von chronischer Autoimmunität führen

Abstract

Not properly cleared dead cells are dangerous for the body. The dead cells accumulate, lose their membrane integrity, danger signals are released, and nuclear antigens get accessible in an inflammatory context. In times of increased apoptosis, tolerance can be broken, a chronic inflammation results which then can lead to an autoimmune reaction against nuclear constituents. An impaired clearance of dying cells represents a central pathogenic process in the development of chronic autoimmune diseases like in systemic lupus erythematosus (SLE). Many adaptor molecules and receptors are involved in the clearance of dying cells. Complement components, serum DNase I, phosphatidylserine, and modified glycoproteins participate crucially in the clearance of apoptotic and necrotic cells. We further observed intrinsic defects of macrophages of some SLE patients. Macrophages as well as granulocytes of some SLE patients showed heterogeneous clearance defects. Furthermore, we observed an accumulation of nuclear material in germinal centres of lymph nodes of some SLE patients. The non-ingested nuclear material may provide survival signals for autoreactive B cells and consecutively antinuclear autoantibodies (ANA) will be produced. We therefore conclude that drugs promoting the phagocytosis are important candidates of specific therapies in the future which expect a more gentle and purposive treatment of patients with SLE.

The Healing of Tibial Fracture and Response of the Local Lymphatic System

“…The noningested nuclear material may provide survival signals for autoreactive B cells and consecutively antinuclear autoantibodies will be produced for wound cells. 11 Taken together, the tibial fracture evokes response of the regional lymphatic system. Normal healing with immune cell infiltrates and foci of ossification is accompanied by dilated lymphatics and enlarged lymph nodes.…”

Sweet taste of cell death: role of carbohydrate recognition systems

“…Cells eventually loose their integrity and release modified apoptotic cell content to milieu that provokes immune response [55][56][57]. Chronic failure of apoptotic cell clearance is now widely accepted to be a primary cause which initiates systemic autoimmunity in diseases such as systemic lupus erythematosus (SLE) [58,59].…”

Das Apoptose-Markerenzym Poly-(ADP-Ribose-)Polymerase (PARP) beim systemischen Lupus erythematodes

“…B. UV-Strahlung) treten beim SLE im Vergleich zu gesunden Kontrollpersonen vermehrt apoptotische Zellen und folglich apoptotisch bedingte Antigene auf [24,33,34,41]. Diese Antigene persistieren aufgrund einer eingeschränkten Phago zytosekapazität und induzieren wiederum die Autoantikörperproduktion [29,33]. Auf diese Weise wird sehr wahrscheinlich ein Circulus vitiosus aufrechterhalten, der letztendlich den Prozess der Autoimmunität ausmachen dürfte [33].…”